The primary objective of this research is to obtain new information on the structural aspects of glomerular filtration in both normal and pathologic glomeruli. Emphasis will be placed on defining the site of the primary filtration barrier(s) for plasma proteins and in establishing the role of the various glomerular components in the filtration process and in the maintenance of the filtration barrier. To achieve these goals we propose to a) analyze the pathways and mechanisms of transport of dextrans across glomeruli from normal animals and from animals with experimental glomerular disease; b) to analyze normal and pathologically altered glomerular structure by freeze-etching; c) to establish sites and rates of incorporation of radioactive amino acid and hexose tracers into glomerular components; and d) to determine the distribution of glomerular basement membrane glycopeptides in normal and abnormal glomeruli. To carry out the work outlined, a combination of morphological (electron microscopy, autoradiography, immunocytochemistry) and biochemical (cell fractionation, gel filtration, tracer incorporation) techniques will be used.